MS treatment related issues

Let us continue to talk about some issues which arise during the treatment of multiple sclerosis.


1) How does the disease pan out: Let me try to give you a broad overview of what to expect if you have been diagnosed with multiple sclerosis. I want to stress that this by no way applies to every patient, because each patient’s disease behaves in its own unique way. Initially as I stated earlier, multiple sclerosis has a remitting and relapsing course. You have an attack, it causes some deficits (weakness, numbess, vision loss or gait and balance problems) and then the attack remits and patient may come back to his or her baseline functioning (meaning there are no residual deficits left behind). When multiple sclerosis behaves in this manner it is said to have a relapsing and remitting course (RELAPSING AND REMITTING MULTIPLE SCLEROSIS OR RRMS).

As the disease progresses though and the patient continues to have more attacks, it is seen that the patient does not remit or revert back to the baseline (meaning that some deficits are left behind like some residual weakness or numbness, some problems with balance, tremors etc). When this occurs the patient starts to incur some disability and the disease is said to enter a progressive course (SECONDARY PROGRESSIVE MULTIPLE SCLEROSIS OR SPMS).

As I stated earlier patients in SPMS stage start to get disabled whether it is due to excessive weakness, fatigue or problems with balance or a disabling tremor. As doctors we try to grade their progression in this stage and there are various scales we use. One of the most commonly used scale is the Expanded Disablility Status Score or EDSS. This is a 10 point scale and when a patient reaches midway like around 5 to 6, he or she starts to need assistance with walking and further on may need a wheelchair for ambulation.

The intention behind using the interferons and other immunomodulatory drugs like copolymer (Copaxone) is to prevent or rather delay the progression from a RRMS to a SPMS.

Hence the rationale behind treating all patients aggressively from the onset. Once the patient is in a SPMS state, the medications are continued and different medications might be added to try to halt and delay the disease progression.


Till now we do not have any drugs which change the natural history of the disease (meaning cure it!!), all we have are medications which may delay the progression.


 There are a certain subgroup of MS patients who have a progressive downhill course right from the onset of the disease (meaning in them the disease does not follow a relapsing and remitting pattern rather they continue to incur more and more neurological deficits). These patients as you can imagine have a poorer outcome and this pattern of disease progression has been referred to PRIMARY PROGRESSIVE MULTIPLE SCLEROSIS OR PPMS


Healthy brain and a healthy mind

Issues that come up during MS treatment

Let us now talk about some issues which come up when you are diagnosed with MS.

1) What happens next?

so you are diagnosed with multiple sclerosis what now? Do you need to start  some multiple sclerosis drug immediately? This is a tough question and something which only your doctor can best decide after reviewing all investigations and MRI brain scans. Multiple sclerosis is in its typical form has a relapsing and remitting course. By that I mean, a patient may present with an acute attack of MS like weakness or unsteadiness or loss of vision in an eye (optic neuritis) but then the attack remits and the patient may come back to his or her baseline with at times no residual signs and symptoms. Then there may be a length of time when the patient experiences no fresh attacks. So the question is when do we start treating the disease. Research has shown that even though the patient may have no clinical attack (no overt manifestations of MS), the disease is still relentless and proceeding in the brain. How do we know this? Simple if you repeat the MRI in even an asymptomatic patient, the MRI shall show new lesions (meaning new plaques are seen in the brain MRI suggesting radiological progression of the disease).

Further research has also shown that these lesions (plaques) in the brain add up and contribute to the final disability. The more the number of plaques in the brain (we refer to this as the plaque burden), the more is the final disability and the cognitive difficulties experienced by the patient.

So now the thinking among MS specialists is to treat early and to treat aggressively. The longer you wait, the more is the damage to the myelin and axons (nerve bundles) in the brain. That said and done each patient’s disease behaves in a unique way. There are a small group of patients who have what is called as benign MS. These patients show little or no disease progression over years both clinically and radiologically. Why some patients have this benign form of the disease no one knows but remember it is very difficult if not impossible to know at the onset if a patient is going to have a benign form of MS or not. Hence usually MS specialists would recommend treating right from the onset.

2) Which interferon to use and which is better?

This is another issue which comes up during MS treatment. There are 3 different kinds of interferon available on the market: interferon beta 1b (marketed as Betaseron) and interferon beta 1a (marketed as Avonex and Rebiff).  Without going too much into detail, there is some evidence to suggest that interferon beta 1 b (Betaseron) may be more effective than interferon beta 1a (Avonex).

Betaseron has to be given three times a week (every alternate day) and it has to be injected subcutaneously (under the skin). Avonex on the other hand needs to be given just once a week and it is given intramuscular (inside the muscle and thus more painful shot than a subcutaneous shot). That said and done since Avonex is given once a week it is far more convenient and does not interfere with a patient’s lifestyle as compared to something which needs to be given three times a week.

There is also the issue of neutralizing antibody formation. Simply put it has been seen that if someone takes interferon for a long time, the body starts to form antibodies against it. These antibodies have been referred to as neutralizing antibodies and if a patient has a high titre of these antibodies, it may neutralize the effect of the interferon (meaning make the interferon less effective). Some research has shown the patient’s who take Betaseron develop neutralizing antibodies at a higher rate as compared to those on Avonex or Rebiff. Again your doctor shall guide you through this decision making process.


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Depression is a relatively common neurological condition. It may occur on its own (as an episode of major depressive disorder or MDD) or it may occur during the course of another chronic neurological illness such as stroke. It is important that depression be recognized and treated since studies have shown that it increases the morbidity and mortality associated with these conditions.

Sometimes it is difficult to weed out which symptoms are due to depression and which due to the organic brain (neurological) condition. Patients who have fronto-temporal dementia (Pick’s disease), Parkinson’s disease, frontal lobe strokes may look depressed. They are akinetic (do not move spontaneously), have mask like emotionless faces and do not talk readily (abulia). On the first glance it may seem they have depression and not an organic neurological condition.

The point I am making is that depression may mask an underlying neurological condition like dementia or a frontal lobe tumor. The reverse is also true, people who have neurodegenerative conditions may have superimposed depression. Upon treating the depression they feel much better and may improve in caregivers rating scales.

The diagnosis of depression is essentially a clinical one. There are certain clinical features which if present for a sufficient length of time usually 2 weeks suffice to make a clinical diagnosis of major depressive disorder (MDD). These features include what is called anhedonia (loss of pleasure in day to day activities), depressed mood ( in children it may present as irritability), weight loss or weight gain, insomnia or hypersomnia (sleeping more than usual), changes in behavior and personality, feeling tired and fatigued, feeling of hopelessness and worthlessness and thoughts of death or sucide.

In a clear cut case no other investigations are warranted but like I stated earlier, at times some organic neurological conditions can present as depression. So to rule out secondary causes of depression, your doctor may order a MRI brain and tests like thyroid function tests (to check if your thyroid hormones are within the normal range–this is usually a simple blood test).

Treatment of depression: Treatment of depresion when it presents along or during the course of a neurodegenerative condition like dementia and Parkinson’s disease is essentially the same as treatment of idiopathic depression (depression which occurs without any organic cause). It involves using drugs. The most commonly prescribed drugs are those which belong to two classes:

1) Tricyclic antidepressants–drugs which belong to this class include medications like Elavil (amitriptyline) and  nortriptyline.

2) Selective Serotonin Reuptake Inhibitors (SSRIs)–drugs include Prozac (fluoxetine) and Paxil (paroxetine) among numerous others.

If a neurological condition is responsible for the depressive symptomatology. example a frontal lobe tumor then removal of that tumor or treatment of the underlying neurological condition is needed. Other treatments that may be attempted include CBT (cognitive behavioral therapy).

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Multiple Sclerosis

Here I shall try to give you a broad overview of Multiple Sclerosis (MS). Multiple sclerosis is a demyelinating disease of the central nervous system (CNS). In the CNS, the axons  are covered by myelin. The axon is the long slender projection of the nerve cell (neuron) that conduct’s nerve impulses away from the body of the cell. The axons in the CNS are coated / covered with myelin, an electrically insulating layer made of phopholipids (a kind of fat). Schwann cells supply the myelin for peripheral neurons ( neurons outside the brain), whereas oligodendrocytes ( a type of cell found in the brain) supply myelin for axons of the CNS.

MS is characterized by demyelination of these axons, that is some process starts to destroy the myelin leading  to loss of myelin. As the disease progresses even axons get destroyed.

Just what sets off this process is still not clear. Various infectious agents and environmental factors have been postulated but none conclusively linked to MS causation.  As a disease MS is more common in Caucasians and more common as you head further from the equator both in the Northern and Southern hemisphere. Thus the incidence of disease is more in Ireland than say in Sub-Saharan Africa. Why you may ask and the answer is no one knows. Maybe it is an environment factor.

Fifteen years of age is the cut off. So if you were born in a country which has a low incidence of MS such as in Asia or Africa and then emigrate to a country with a higher incidence of MS such as Ireland or Canada after the age of 15, you shall carry that low risk of the country of birth with you but if you emigrated say around 6 years then your risks of developing MS go up to the risk of a native in Ireland or Canada.

MS is more common in women as compared to men but when it does occur in men it is usually more severe.

Clinical presenting features of MS-MS has been rightly called the great mimicker in neurology. It can present with a myriad of clinical signs and symptoms which are referrable to both the brain as well as the spinal cord. MS typically presents in the following ways:

1) Isolated attack of optic neuritis: the usual history is a young to middle aged woman who presents with sudden and rapid onset of loss of vision in one eye at times associated with pain on moving the eyes. This occurs due to demyelination of the optic nerve (the nerve which is involved in vision). If the attack remains confined to the optic nerve, this is referred to as a Clinically Isolated Syndrome (CIS). Not all patients with a CIS go on to develop MS, as there are other causes of optic neuritis besides MS.

2) Numbness or weakness in one part of the body.

3) Visual complaints like double vision (diplopia), eyes not moving well (weakness of a muscle of the eye).

4) problems with balance and coordination.

5) ataxia and tremors (patients have a prominent tremor in their hands or in their trunk, as well as are off balance while standing or walking). This is due to involvement of the cerebellum and cerebellar pathways by the MS demyelinating process.

6) problems with bladder control leading to urinary incontinence.

7) Weakness in the legs (paraplegia or paraparesis)–if MS involves the spinal cord, it may cause weakness of both the legs. This condition is referred to transverse myelitis or transverse myelopathy.

So what are the presenting features of MS? MS can present in various fashions, at times the presenting features are vague and this may lead to a delay in diagnosis. The commom presenting features of MS are as follows:

1) MS may present acutely as an attack of optic neuritis. Opitic neuritis is inflammation of the optic nerve and hence the patient seeks medical attention for acute loss of vision and pain in the eye. If this occurs in a young women or man, MS should be borne in mind though there are numerous other causes of loss of vision. Patient may also complain of a desaturation of the color red ie the color red does not appear as bright and ” red” as it used to.

All attacks of optic neuritis do not necessarily lead to MS. Hence this limited presentation at onset is referred to by doctors as a ” clinically isolated syndrome“.

To be certain that your presentation is indeed isolated, your doctor shall have to take a thorough history to make sure you have never had any other attacks suggestive of MS in the past. MRI of the brain and spine as well examination of the cerebro spinal fluid is carried out to rule out any other silent lesions of MS. If no other lesions/ plaques of MS are found in the brain or spinal cord on MRI and the spinal fluid comes back normal then and only then one has a clinically isolated syndrome.

Patients who have a clinically isolated syndrome do not warrant treatment with MS specific drugs like interferons. Your doctor might give you a short course of IV and oral steroids to hasten the recovery of eye function. Most patients who have optic neuritis regain their visual acuity.

2) Numbness or weakness in an arm or leg; patients with MS may present initially with complaints of numbness or weakness in an arm or leg. This usually occurs due to involvement of motor and sensory pathways in the brain or spinal cord by MS lesions.

3) Weakness in legs: if the MS lesions involve the spinal cord, patients may present with more symmetrical involvment like numbness or weaknes in both legs (paraparesis). This condition in which MS lesions are seen in the spinal cord is referred to acute transverse myelitis.

4) Problems with balance and incoordination; MS lesions frequently involve those parts of the brain which control balance and coordination (cerebellum). Thus MS patients frequently have problems with balance and are ataxic ( drunken like gait). They have a prominent tremor in their hands and feet especially when they try to reach out to touch something. These problems with gait and balance are one of the major causes of disability and morbidity in patients with MS.

5) urinary incontinence and sexual dysfunction: MS patients may experience erectile dysfunction and urinary incontinence is very common in female MS patients.

6) Double vision: MS patients may complain of seeing double (diplopia), this occurs due to involvement of tracts in the brain which control eye movements ( an example of such a tract which is frequently involved in MS is medial longitudinal fasiculus or MLF)

Thus as you can imagine MS can present with a myriad of symptoms and the diagnoisis may not be made at the first presentation. It is usually a constellation of signs and symptoms which do not localize to any one particular area in the brain or spinal cord which makes doctors think of MS as the differential diagnosis.

Thus as I stated earlier MS is a disease which is characterized by plaques (MS lesions) which are disseminated in space ( different areas in brain and spinal cord) and time (clinical attacks occur at different times in a person’s lifetime).


Diagnosis: how is the diagnosis of MS finally confirmed? Let us discuss that now. As I stated earlier if you present with certain clinical signs and symptoms your doctor may entertain the diagnosis of multiple sclerosis.

Now once the diagnosis is entertained how do you go about confirming the diagnosis. This is usually done with the aid of an MRI of the brain and spinal cord which may show the characteristic plaques of demyelination. Your doctor may also want you to get a spinal tap (lumbar puncture). Lumbar puncture or LP is a test where in a needle is inserted into your lower back to get some of the cerebro-spinal fluid (CSF). About 10-15 ml of CSF is usually removed and sent to the laboratory for various tests. We look for some markers of MS in the CSF. If they are present, they strengthen the case for MS. At times, tests like MRI brain and spinal cord as well as lumbar puncture are unrevealing or non-diagnostic, in that case your doctor may order other tests like visual evoked potential (VEP) and somatosensory evoked potential (SSEP).

Certain diseases like for example Lyme disease, sarcoidosis can mimick MS in their presentation both clinically as well as on the MRI. Hence in appropiate circumstances more tests may be ordered to rule out these conditions.


Treatment of Multiple Sclerosis: There are now many treatments available for MS. Here I shall list a few of them without going into too much detail.

Treatment of an acute attack of MS: patients may present to the hospital with an acute attack of MS. This may involve an acute episode of optic neuritis presenting with pain and visual loss in the affected eye or they may present with increased weakness or lethargy. Acute attacks of MS respond well to corticosteroids. Usually steroids are given intravenously at high doses for about 3-5 days. Steriods help in aborting the attack and hasten recovery but they do not change the natural history of the disease (meaning that the MS disease process still continues its relentless progression).

To change the natural history of the disease, drugs that modulate the immune system are used. The most commonly used drugs are :

1) Interferons–usually interferon beta 1 b or interferon beta 1 a. Interferon beta 1 b comes by the brand name of Betaseron while interferon beta 1 a comes by two brand names: Avonex and Rebiff. When compared to each other, the interferons have some difference with respect to potency, easy and frequency of administration. You doctor shall help decide which interferon is best for you. All the interferons have some common side-effects namely injection site reactions, depression, hypothyroidism etc.

2) Glatiramer acetate also called Copolymer 1 -marketed under the brand name Copaxone.

3) Mitoxantrone

4) Natalizumab marketed under the brand name Tysabri